Primary and metastatic solid tumors comprise cancer cells, host cells such as endothelial cells and fibroblasts, and inflammatory immune cells. Yet, although individual cancer cells may exhibit a stable signature of protein marker expression (S. Ramaswamy et al., Nat. Genet. 33, 49 (2003); B. S. Taylor et al., Cancer Res. 66, 5537 (2006)), tumors in general are highly adaptive and heterogeneous (S. Maheswaran et al., N. Engl. J. Med. 359, 366 (2008); D. Hanahan and R. A. Weinberg, Cell 100, 57 (2000)) and thus may respond differently to therapeutics based on stochastic differences in protein expression across the cancer cell population (S. L. Spencer et al., Nature 459, 428 (2009)). It is therefore becoming clear that molecular diagnosis using cancer cells will yield critical information for classifying tumors, stratifying patients for molecular targeted therapies and for assessing treatment efficacy (D. D. Von Hoff et al., J. Clin. Oncol. 28, 4877 (2010)). Expanding knowledge of the proteome in clinically harvested cancer cells may also yield new information about tumor biology (D. J. Brennan et al., Nat. Rev. Cancer 10, 605 (2010)).
Within a clinical setting, cancer cells from primary tumors are typically obtained through image-guided intervention or open surgical procedures (W. Bruening et al., Ann. Intern. Med. 152, 238 (2010)). Percutaneous biopsy is a well-established clinical procedure that yields cells for cytology using 22-gauge (22 G) fine-needle aspirates, and small tissue fragments for histology by core biopsies using 16 G to 19 G needles. Samples are commonly processed using conventional histological stains before immunohistochemical evaluation if sufficient tissue remains (tissue sections contain billions of cells). However, immunohistochemical evaluation is only semiquantitative, time-consuming, and technically challenging.